The Lower Homologs

The ring-contracted analog of alphaprodine is prepared by a variation of the scheme above. Alkylation of 109 with ethyl bromoacetate affords the lower homolog diester (115). Dieckmann cyclization followed by saponification-decarboxylation yields the pyrrolidine (116). Reaction with phenylmagnesium bromide leads to the condensation product (117) acylation with propionic anhydride gives the analgesic agent prolidine (118)... 

Azetidine-2-carboxylic acid, the lower homolog of proline, has been isolated from Convallaria majalis (lily of the valley) 40,44), Polygonatum officinalis (Solomon s seal) 153), and Polygonatum multiflorum 45). Fowden and Steward 47) surveyed plants from 56 genera for nitrogenous compounds and found azetidine-2 -carboxylic acid to be restricted to members of the Liliaceae. In some species it was identified in leaf, stem, and root but was more commonly found in the seed. In Polygonatum, azetidine-2-carboxylic acid accounted for 75% or more of the total nonprotein nitrogen in the rhizome 45). There was no evidence that it occurred as a constituent of protein. 

The first report on the liquid crystalline properties of these compounds was published by Gray and Mosley [44] in 1976. The series of 4 -n-alkyl-4-cyanobiphenyls (CBn) have been widely studied by different methods due to their readily accessible nematic ranges around room temperature. The compounds have the phase sequences crystal-nematic-isotropic for CBS, CBIO, and monotropic nematic for CBS, CB4 crystal-smectic A-nematic-isotropic for CB9 crystal-smectic A-isotropic for CBll. The lower homologous CB2 is nonmesogenic. The general chemical structure of the compounds CBn is presented in Fig. 1. 

Dipolar cycloaddition of betaines 492 gave cycloadducts 493, which produced tricyclic compounds 494 on further thermolysis (Scheme 48) <1995H(41)1631>. Heating 9,9-disubstituted yr/ra-(4-hydroxy-2-oxo-2//-pyrido-[2. -//][ 1.3]thiazinium) hydroxides 495 afforded tricyclic compounds 497 as diastereomeric mixtures (Scheme 49) <1995S973>. In the case of the lower homolog (n = 0), a cycloadduct 496 could be also isolated at lower temperature. 

Crotyl diazoacetate has been prepared by the procedure described here and by the reaction of diazomethane with crotyl chloroformate. The lower homolog, allyl diazoacetate, has been )repared by the reaction of allyl glycinate with nitrous acid and by the successive conversion of allyl chloroacetate to the corresponding azide, iminophosphorane, and, finally, the diazo ester. ... 

Nearly all the disubstituted oxadiazoles mentioned in the literature contain at least one aromatic substituent. The fact that purely aliphatic derivatives have not been isolated until recently is obviously due to the difficulty of isolating these compoimds. The lower homologs are very volatile and cannot be separated by distillation from usual solvents. Dimethyloxadiazole, for instance, the synthesis of which was attempted by Nordmann in 1884 60), was only "perceived" through its odor only in 1959 could this product be identified after its isolation by salting out from an aqueous solution (5, 44 c). 

In general, only helicenes with six or more benzene or other rings will be treated. The lower homologs, dibenzo[c,g]phenanthrene (pentahelicene) and benzo[c]phen-anthrene will only be mentioned for comparison in some instances. 

The methiodide is prepared from 2,3-dimethylbenzyldi-methylamine according to the procedure for producing the lower homolog.1... 

The solvolysis of 7,7-dibromo-bicyclo[4.1.0]heptane in methanol in the presence of silver perchlorate leads to ( -2-bromo-3-methoxycyeloheptene [172, 173]. A more detailed study of this reaction — having been performed by Ito in 1986 [174] — has revealed that the stereochemical result of the solvolysis depends on the length of the polymethylene chain in these bicyclic dihalides. For the lower homologs (n = 2 to 4) it is the ( )-isomer XIII that is produced, whereas for the more extended systems (n = 5 to 8) the Z-bromoethers XIV are produced. 

Aliphatic Nitro Compounds The molecular ion peak (odd number) of an aliphatic mononitro compound is weak or absent (except in the lower homologs). The main peaks are attributable to the hydrocarbon fragments up to M — N02. Presence of a nitro group is indicated by an appreciable peak at m/z 30 (NO+) and a smaller peak at mass 46 (N02+). 

Only small amounts of side products are formed. The purity of the acid is mostly greater than 98%, the major side product (up to 2%) is the lower homologous carboxylic acid. 

Unsubstituted aliphatic carboxylic acids are only very slowly further oxidized to the lower homologous acid in the oxidation of primary alkanols less than 2% of this acid are found. However, with substituted carboxylic acids the cleavage can become the main reaction. Thus anodic oxidation of phenylacetic acid at the nickel hydroxide electrode leads to 87% benzoic acid . Cleavages of similar to a lesser extent are observed with amino acids (Chapter 3.1) or P-alkoxy substituted acids (Chapter 2.4). 

UV, 1H, and 13C NMR investigations revealed that 5,7,8,9-tetrahydro and 1,2,3,4,5,7,8,9-octahydro tautomeric forms are predominant for 6-ethoxalyl derivatives 23 and 24, while the lower homologs, the pyrrolidino[2,l-Z>]-quinazolin-10-ones, exist in the enol-imine forms [89JCS(P2)1613]. 

The importance for homoallylic participation of the exact position-of-lhe p orbitals of the double bond in relation to the developing p arhital at the-reartinn site li-also shown by the rate change attendant on puckering of the five-mem-bered ring in the series, 54, 55, and 56.70 In the lower homologs of these bi-... 

Figure 10. Field desorption mass spectra recorded at 23-24 ma for samples of (A) N-stearoyl dihydroglucocerebroside and (B) N-stearoyl dihydrolactocerebroside. (Both samples contain small amounts of the lower homolog H-palmitoyl fn = 14).

On the other hand, reaction of the disilacycloheptane (XIV n = 5) with sulfuric acid is not so energetic as that of the lower homologs and gives two major products with the silicon-silicon bond intact, (XVIII) and (XIX), in the ratio of about 1 1, along with three minor ones, (XX), (XXI), and (XXII). Only the last compound is a product arising from cleavage of the silicon-silicon bond. 

Pyrazole and the lower homologs dissolve readily in the majority of organic solvents and in water. The solubilities of pyrazole at 25° in water, benzene, and cyclohexane (expressed as gm/100 gm of solvent)... 

Contaminants may arise from impure starting materials, incomplete reactions and secondary reaction products. A knowledge of these factors serves to limit the list of probable contaminants to a small number. Tentative identifications of some of the contaminants shown as minor peaks in the chromatograms were assigned by matching their retention times (or retention temperatures) with those of probable contaminants. In the case of the six carboxylic acids of Table II, the contaminants are known to be carboxylic acids, since the method of purification involves repeated precipitations as the ammonium salts. The tridecanedioc acid observed in the octadecanedioc acid (compound 10 of Table IV) is considered the source of the lower homolog impurity to-(p-chlorophenyl)-octadecyl bromide (compound 6 of Table IV). 

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